Clinical Practice Guideline by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA): 2021 Focused Update Guidelines on Management of Clostridioides difficile Infection in Adults

Abstract

This clinical practice guideline is a focused update on management of Clostridioides difficile infection (CDI) in adults specifically addressing the use of fidaxomicin and bezlotoxumab for the treatment of CDI. This guideline was developed by a multidisciplinary panel representing the Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America (SHEA). This guideline is intended for use by healthcare professionals who care for adults with CDI, including specialists in infectious diseases, gastroenterologists, hospitalists, pharmacists, and any clinicians and healthcare providers caring for these patients. The panel’s recommendations for the management CDI are based upon evidence derived from topic-specific systematic literature reviews. Summarized below are the recommendations for the management of CDI in adults. The panel followed a systematic process which included a standardized methodology for rating the certainty of the evidence and strength of recommendation using the GRADE approach (Grading of Recommendations Assessment, Development, and Evaluation). A detailed description of background, methods, evidence summary and rationale that support each recommendation, and knowledge gaps can be found online in the full text.

Clostridioides difficile, guidelines, CDI

I. IN PATIENTS WITH AN INITIAL Clostridioides difficile INFECTION EPISODE, SHOULD FIDAXOMICIN BE USED RATHER THAN VANCOMYCIN?

Recommendation:

1. For patients with an initial Clostridioides difficile infection (CDI) episode, we suggest using fidaxomicin rather than a standard course of vancomycin (conditional recommendation, moderate certainty of evidence). Comment: This recommendation places a high value in the beneficial effects and safety of fidaxomicin, but its implementation depends upon available resources. Vancomycin remains an acceptable alternative.

II. IN PATIENTS WITH RECURRENT CDI EPISODE(S), SHOULD FIDAXOMICIN BE USED RATHER THAN VANCOMYCIN?

Recommendation:

1. In patients with recurrent CDI episodes, we suggest fidaxomicin (standard or extended-pulsed regimen) rather than a standard course of vancomycin (conditional recommendation, low certainty evidence). Comment: Vancomycin in a tapered and pulsed regimen or vancomycin as a standard course are acceptable alternatives for a first CDI recurrence. For patients with multiple recurrences, vancomycin in a tapered and pulsed regimen, vancomycin followed by rifaximin, and fecal microbiota transplantation are options in addition to fidaxomicin.

III. IN PATIENTS WITH A CDI EPISODE, SHOULD BEZLOTOXUMAB BE USED AS A CO-INTERVENTION ALONG WITH STANDARD-OF-CARE ANTIBIOTICS RATHER THAN STANDARD-OF-CARE ANTIBIOTICS ALONE?

Recommendation:

1. For patients with a recurrent CDI episode within the last 6 months, we suggest using bezlotoxumab as a co-intervention along with standard-of-care (SOC) antibiotics rather than SOC antibiotics alone (conditional recommendation, very low certainty of evidence). Comment: This recommendation places a high value on potential clinical benefits, but implementation is often limited by feasibility considerations. In settings where logistics is not an issue, patients with a primary CDI episode and other risk factors for CDI recurrence (such as age ≥65 years, immunocompromised host [per history or use of immunosuppressive therapy], and severe CDI on presentation) may particularly benefit from receiving bezlotoxumab. Data on the use of bezlotoxumab when fidaxomicin is used as the SOC antibiotic are limited. The Food and Drug Administration warns that “in patients with a history of congestive heart failure (CHF), bezlotoxumab should be reserved for use when the benefit outweighs the risk.”

Notes

Disclaimer. It is important to realize that guidelines cannot always account for individual variation among patients. They are assessments of current scientific and clinical information provided as an educational service; are not continually updated and may not reflect the most recent evidence (new evidence may emerge between the time information is developed and when it is published or read); should not be considered inclusive of all proper treatments, methods of care, or as a statement of the standard of care; do not mandate any particular course of medical care; and are not intended to supplant physician judgment with respect to particular patients or special clinical situations. Whether and the extent to which to follow guidelines is voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient’s individual circumstances. While IDSA and SHEA make every effort to present accurate, complete, and reliable information, these guidelines are presented “as is” without any warranty, either express or implied. IDSA and SHEA (and its officers, directors, members, employees, and agents) assume no responsibility for any loss, damage, or claim with respect to any liabilities, including direct, special, indirect, or consequential damages, incurred in connection with these guidelines or reliance on the information presented. The guidelines represent the proprietary and copyrighted property of IDSA. Copyright 2021 Infectious Diseases Society of America. All rights reserved. No part of these guidelines may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of IDSA. Permission is granted to physicians and healthcare providers solely to copy and use the guidelines in their professional practices and clinical decision making. No license or permission is granted to any person or entity, and prior written authorization by IDSA is required to sell, distribute, or modify the guidelines, or to make derivative works of or incorporate the guidelines into any product, including but not limited to clinical decision-support software or any other software product. Except for the permission granted above, any person or entity desiring to use the guidelines in any way must contact IDSA for approval in accordance with the terms and conditions of third-party use—in particular, any use of the guidelines in any software product.

Acknowledgments. The expert panel expresses its gratitude for thoughtful reviews of an earlier version by Drs. Clifford McDonald, Timothy Planche, and Kelly Reveles. The panel thanks Genet Demisashi and Rebecca Goldwater for their continued support throughout the guideline process. The panel also expresses gratitude to librarian Shandra Knight for her continued literature support throughout the development of the guideline.

Financial support. Support for this guideline was provided by the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America.

Potential conflicts of interest. The following list is a reflection of what has been reported to IDSA. To provide thorough transparency, IDSA requires full disclosure of all relationships, regardless of relevancy to the guideline topic. Evaluation of such relationships as potential conflicts of interest is determined by a review process which includes assessment by the Standard and Practice Guidelines Committee (SPGC) Chair, the SPGC liaison to the development panel, and the Board of Directors liaison to the SPGC, and if necessary, the Conflict of Interest (COI) Ethics Committee. The assessment of disclosed relationships for possible COIs is based on the relative weight of the financial relationship (ie, monetary amount) and the relevance of the relationship (ie, the degree to which an association might reasonably be interpreted by an independent observer as related to the topic or recommendation of consideration). The reader of these guidelines should be mindful of this when the list of disclosures is reviewed. K. W. G. has served as a consultant/advisor to Merck and Synthetic Biologics; receives research grants from Summit Therapeutics, Paratek Pharmaceuticals, Acurx Pharmaceuticals, Tetraphase Pharmaceuticals, and the National Institutes of Health (NIH); and has received research grants from Tetraphase Pharmaceuticals. S. J. serves as an Advisory Board member for Bio-K+ and Acurx Pharmaceuticals; receives renumeration from Pfizer as a member of the Data Monitoring Committee and Ferring Pharmaceutical in developing an education monograph for transition of care for C. difficile; has served as an Advisory Board member for Cutis Pharma and Summit Therapeutics; and served on the Steering Committee for Synthetic Biologics. C. P. K. serves as an advisor for Matrivax, Vedanta, Merck, Cour, Acurx Pharmaceuticals, Finch, Microbiota, and Milky Way Life Science; has served as an advisor for Artugen, Glutenostix, Innovate, and Sanofi; receives honoraria from Merck for serving as a symposium speaker; has received honoraria from Biocodex for serving as a symposium speaker; has held stock in Glutenostix; receives research funding from the NIH and the National Institute of Allergy and Infectious Diseases; has received research funding from Instit Merieux, Merck, and Allergan; currently serves as the President of the Society for the Study of Celiac Disease and as the Secretary for the Foundation for Celiac Disease Outcome Measures; and his organization, Beth Israel Deaconess Medical Center, has received organizational benefits from the Sydney Frank Foundation and Milky Way Life Sciences. V. L. has received past research funding from the Fonds de Recherche du Québec Research (FRQ-S). A. M. S. has received honoraria from the American Society of Health-System Pharmacists. M. H. W. serves as an advisor for Summit and Seres; has served as an advisor for Merck and Astellas; receives research grants from Summit, Seres, the Centers for Disease Control and Prevention, the NIH, the UK Medical Research Council, and the European Union Innovative Medicines Initiative; and has received research grants from Merck and Astellas. A. J. G.-L. reports no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.